2024-03-29T08:47:53Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/547802022-11-17T02:08:08Zhdl_2115_20044hdl_2115_124In vitro optimization of 2 '-OMe-4 '-thioribonucleoside-modified anti-microRNA oligonucleotides and its targeting delivery to mouse liver using a liposomal nanoparticleTakahashi, MayumiYamada, NaokiHatakeyama, HirotoMurata, ManamiSato, YusukeMinakawa, NoriakiHarashima, HideyoshiMatsuda, Akira499MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post-transcriptionally. Previous studies, which characterized miRNA function, revealed their involvement in fundamental biological processes. Importantly, miRNA expression is deregulated in many human diseases. Specific inhibition of miRNAs using chemically modified anti-miRNA oligonucleotides (AMOs) can be a potential therapeutic strategy for diseases in which a specific miRNA is overexpressed. 2'-O-Methyl (2'-OMe)-4'-thioRNA is a hybrid type of chemically modified oligonucleotide, exhibiting high binding affinity to complementary RNAs and high resistance to nuclease degradation. Here, we evaluate 2'-OMe-4'-thioribonucleosides for chemical modification on AMOs. Optimization of the modification pattern using a variety of chemically modified AMOs that are perfectly complementary to mature miR-21 revealed that the uniformly 2'-OMe-4'-thioribonucleoside modified AMO was most potent. Further investigation showed that phosphorothioate modification contributed to long-term miR-122 inhibition by the 2'-OMe-4'-thioribonucleoside-modified AMO. Moreover, systemically administrated AMOs to mouse using a liposomal delivery system, YSK05-MEND, showed delivery to the liver and efficient inhibition of miR-122 activity at a low dose in vivo.Oxford univ pressJournal Articleapplication/pdfapplication/pdfhttp://hdl.handle.net/2115/54780https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/54780/1/WoS_64354_Matsuda_Akira.pdfhttps://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/54780/2/WoS_64354_Matsuda_Akira_Supplementary_Data.pdf0305-1048Nucleic acids research412210659106672013-12enginfo:pmid/24030710info:doi/10.1093/nar/gkt823publisher